Inotrope therapy in acute heart failure: a critical review of clinical and scientific evidence for levosimendan in the context of traditional treatment

The clinical heterogeneity of acute heart failure and the low number of controlled trials, to date, are the main causes of the lack of agreement on therapeutic objectives, uncertainty on the most appropriate management, and difficulties to obtain robust evidence for the treatment of this syndrome. The inappropriate use of inotropic agents is one the most common pitfalls shown by registries. Two to 10% of patients admitted for acute heart failure present with a low output syndrome, a clinical profile associated with high mortality, where inotropes may be a rational therapeutic choice. Crucial points for an effective use of inotropes are an accurate evaluation and selection of patients, tailoring of therapeutic schemes and strict patient monitoring. Beta-adrenergic agonists and phosphodiesterase inhibitors increase myocardial oxygen demand, favor arrhythmias and may cause peripheral vasodilation with a secondary decrease in coronary perfusion pressure. These effects may translate in myocardial ischemia, loss of cardiomyocytes and accelerated ventricular remodeling with worse prognosis. Levosimendan, a novel inotropic agent studied according to the principles of evidence-based medicine, augments myocardial contractility without changes in intracellular calcium concentrations, and with minimal impact on myocardial oxygen consumption. This paper, based on an expert consensus, aims to suggest criteria for the appropriate use of inotropic agents in acute heart failure, based on a critical appraisal of the existing evidence and clinical experience.